Since the time that a method whereby faint near infrared rays (700–1300 nanometers) are irradiated from on the skin of the head through the skull into the brain to measure changes in concentration of oxygenated hemoglobin (Oxy-Hb; HbO2) and changes in concentration of deoxygenated hemoglobin (Deoxy-Hb; Hb) in the blood at the brain surface (cerebral cortex) just inside the skull was proposed by F. F. Jobsis in 1977, research on the measurement of tissue oxygen concentration by means of this near-infrared spectroscopy (NIRs) method has progressed rapidly.
The near-infrared spectroscopy method has the advantages that metabolism of separate tissues can be measured non-invasively (non-invasiveness), that this can furthermore be implemented with a simple and convenient apparatus (portability), and that, unlike PET (positron emission CT), f-MRI (functional magnetic resonance imaging) and the like, it additionally makes possible the real-time measurement of changes in tissue metabolism in the brain, muscles and the like over time (temporality); and it has given rise to expectations of a wide range of application, such as in monitoring brain function, evaluating muscle rehabilitation in physical therapy, and use in exercise physiology.
The present inventor and his colleagues conducted light stimulus experiments in humans in which the brain was partially irradiated with near infrared light, and as a result, showed that the distribution of localized brain function can be monitored at the bedside, and proved that imaging of local brain function using this bedside method of non-invasive detection of local brain function is possible (Toshinori Kato, Sachio Takashima, “NIR Spectroscopy ni yoru kyokusho nouketsuryu hendou no kansatsu”, Shinshinshougaiji(sha) no iryou ryouiku ni kansuru sougouteki kenkyu no houkokusho [“Observation of variation in local brain blood flow by means of near-infrared spectroscopy”, in Comprehensive Research Report Concerning Medical Care for Children (People) with Disabilities] (Japan Ministry of Health and Welfare), p. 179–181 (1992); Kato T, Kamei A, et al., “Human visual cortical function during photic stimulation monitoring by means of near-infrared spectroscopy”, J Cereb Blood Flow Metab. 13:516–520 (1993). This is the pioneering work on the technology for graphic display of functional topography of the brain surface in the front and back of the head (the mapping of hemoglobin distribution, i.e., the display of variation in blood volume, reflecting brain activity, as a topographical map).
Examples of subsequent technology for the graphic display of brain function include the inventions described in Japan published patent applications No. H9-149903, No. 2001-212115 and No. H9-238914. The inventions described in these publications concern apparatus for measuring the interior of a living body by irradiating the living body with near infrared light from a plurality of irradiation sites and detecting light transmitted through the living body at a plurality of detection sites; this is called Optical Topography (registered trademark), and it calculates changes in concentration of oxygenated hemoglobin and deoxygenated hemoglobin in the blood at each measuring point, based on light intensity signals measured at a plurality of measuring points, and displays them topographically.
Because the oxygen partial pressure of the capillaries is approximately equal to that of the tissue, it is conventionally accepted that in measuring tissue oxygen concentration, it is extremely important to collect capillary blood oxygen concentration data. The near-infrared spectroscopy method, however, takes measurements non-invasively, from the surface of the body, and because changes in the signal are thus the sum of reactions occurring in the regions existing on the light path, its quantifiability, i.e., spatial resolution, is considered to be inferior. The data shown in FIG. 1(a) was conventionally accepted as predominantly capillary data, as clearly shown in the literature by H. Marc Watzman et al. (“Arterial and venous contributions to near-infrared cerebral oximetry”, Anesthesiology 2000;93:947–53) and FIG. 8 of Japan published patent application H9238914, but the present inventor believes that this is inevitably predominantly venous data, by reason of the facts that it was obtained by measuring a site where a vein typically exists on the light path and that the apparatus was configured with wide spacing (approximately 30 mm) between the measuring points.
This is because the capillaries are structured in such a way that application of stimulus easily results in a divergence between red blood cell variation and blood serum component variation. Namely, in the capillaries, the red blood cells and the serum move at different speeds, changes in the hematocrit or changes in total hemoglobin are therefore more likely to occur there than in the veins, and consequently, mirror-image changes in oxygenated hemoglobin and deoxygenated hemoglobin are less likely to occur there than in the veins. Predominantly capillary data is therefore considered necessarily to be that in FIG. 1(b), which shows an asymmetrical mode of change, because of the conclusions obtained in the research of the present inventor. If this is the case, then conventional measuring apparatus can be said to be configured based on an erroneous theoretical understanding.
Additionally, even in the rare case when a conventional measuring apparatus recognizes the data shown in FIG. 1(b) as true predominantly capillary data, because the characteristics of change over time for both predominantly capillary data and predominantly venous data are macroscopically approximated before the application of stimulus (including both internal stimuli from physiological effects and external stimuli)—that is, at rest, before changes occur in the tissue (in the figures, baseline=the period up to approximately 8 seconds)—when this data is compared with the predominantly venous data of FIG. 1(a) it is impossible to tell whether the data being collected is predominantly capillary data or predominantly venous data during the period up until changes occur in the tissue, using a conventional measuring apparatus, which is confined to the output of FIGS. 1(a) and (b). Taking this time lag together with the extremely low probability of collecting capillary data because of the wide setting of the measuring point spacing (approximately 30 mm), gives rise to low expectations of a sufficient contribution to on-site medicine.
In addition, because conventional measuring apparatus only measure changes in oxygenated hemoglobin and deoxygenated hemoglobin concentration (and this data is highly inaccurate), and because theories of brain physiology, such as the interrelationships between these data and vasodilatation/vasoconstriction occurring in the capillaries, and the involvement of hematocrit changes and the oxygen extraction rate in the capillaries accompanying changes in total hemoglobin, have not been adequately clarified, these apparatus therefore remain in the realm of simple scientific experimental tools, as monitors showing changes in concentration of hemoglobin and the like, and monitors showing changes in oxygen concentration.
The present invention accordingly takes into consideration the above-stated problems, and takes as its subject the provision of an apparatus for evaluating biological function that, in differentiating as far as possible information from the capillaries, which reflects tissue metabolism, from information from outside the tissue (for example, the arteries and veins), has high speed and accuracy enabling it to compensate for the low spatial resolution of conventional near infrared spectroscopy methods, and that furthermore does not merely monitor changes in oxygen concentration and the like, but makes it possible to easily and conveniently distinguish between capillary reactions, metabolic reactions and the like.